2013 — 2018 |
Bateman, Jack |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Career: Mechanisms of Cis-/Trans-Promoter Competition in Drosophila
Intellectual Merit: Physical contacts between chromosomes, known as interchromosomal interactions, are observed in interphase nuclei of diverse species. In some cases, these interactions allow regulatory elements to act in trans, modulating the expression of genes encoded on a separate chromosome held in close proximity. The advent of high-throughput genome-wide analyses of chromosomal conformations has vastly accelerated the rate at which interchromosomal interactions can be cataloged; however, the functional characterization of their genetic consequences has lagged behind. This CAREER project helps to fill the "function gap" by developing a comprehensive understanding of how a gene expression enhancer will behave when it encounters potential gene regulatory promoters on separate but nearby chromosomes. The experiments center on the creation of transgenic Drosophila carrying various fluorescent reporters that act as readouts for the impacts of interchromosomal interactions on gene expression. These experiments will provide a better understanding of the parameters governing enhancer action in trans, providing information on how the spatial organization of the nucleus impacts enhancer-promoter specificity.
Broader Impacts: The education plan of this project is focused on expanding research opportunities and hands-on experience in genetics and molecular biology for undergraduate students. Specifically, the project will 1) develop a research-based lab module for an undergraduate genetics course, 2) offer an annual workshop for undergraduate students from a local community college, 3) partner with an existing program that introduces research opportunities to students from underrepresented groups, and 4) provide opportunities for independent research for undergraduates from diverse backgrounds.
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0.915 |
2019 |
Bateman, Jack |
R15Activity Code Description: Supports small-scale research projects at educational institutions that provide baccalaureate or advanced degrees for a significant number of the Nation’s research scientists but that have not been major recipients of NIH support. The goals of the program are to (1) support meritorious research, (2) expose students to research, and (3) strengthen the research environment of the institution. Awards provide limited Direct Costs, plus applicable F&A costs, for periods not to exceed 36 months. This activity code uses multi-year funding authority; however, OER approval is NOT needed prior to an IC using this activity code. |
Know Your Neighbors: Investigating the Influence of Gene Co-Localization On Transcriptional Dynamics
In the crowded and dynamic three-dimensional space of the nucleus, active genes often share local neighborhoods with one another. Despite significant recent progress in analyses of 3D positioning of genes, it is not yet fully understood how the co-localization of genes plays a role in their transcriptional output. The long-term goal of this research is to understand how a gene?s expression is influenced by its neighbors in space and time. The study of how co-localized genes share local resources has the potential to shed significant light on fundamental mechanisms of transcription, but progress has been severely limited by a reliance on methods that examine transcription and 3D position separately in fixed or disrupted tissues. The objective of this proposal is to uncover the impact of gene co-localization on transcriptional dynamics in living cells to provide a dynamic spatiotemporal quantification of transcription for genes that share a local 3D neighborhood. To address this objective, the proposal focuses on Drosophila melanogaster and takes advantage of a phenomenon called transvection, where sequences at allelic positions on homologous chromosomes are stably co-localized via a process called somatic homolog pairing. Furthermore, the proposed experiments employ the MS2 and PP7 systems for live analysis of transcriptional dynamics, which permit simultaneous quantification of transcriptional activity and assessment of the 3D positions of genes over time in living cells. The central hypothesis guiding the proposal is that co-localization of genes via somatic homolog pairing will result in the sharing of local stores of resources necessary for transcription, which can be understood by analyzing how co-localization influences the parameters of transcriptional dynamics, including the frequency, duration, and amplitudes of transcriptional bursts. This hypothesis is tested in the context of two contrasting scenarios resulting from co-localization of genes via transvection: in one scenario, co-localized promoters in cis and in trans to an enhancer compete for activation, while in a second scenario, co-localized enhancers cooperate to achieve augmented levels of transcriptional output. The proposed experiments have the expected outcome of identifying precisely and quantitatively how interactions between co- localized genes influence transcriptional dynamics, providing key insights into mechanisms by which 3D genome organization controls gene expression.
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0.915 |